Patient Case Presentation

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Patient Case Presentation

• Neurosurgery Red Service
• Gabriel Zada, MD
• Sean McNatt, MD
• LAC-USC Medical Center
• May 24, 2006

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Patient J.P.

• History of Present Illness
• 22 year old caucasian female
• Long history of headaches
• Presented with 2 days of
• Sinus headache progressing to
• Bifrontal headache
• Somnolence
• Altered mental status
• Nausea/vomiting
• No fevers, chills
• No history of trauma

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Patient J.P.

• Past Medical History
• Headaches x 2 years
• Otherwise unremarkable past medical history
• Medications
• None
• Allergies
• None Known
• Social History
• Mother of a 2 year old child
• No tobacco, drug, or alcohol use

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Patient J.P.

• Physical Exam
• Mental Status
• Patient somnolent, partially arousable
• Oriented inconsistently to name only
• Responds inappropriately with one word responses
• Cranial Nerve Exam
• Right partial ptosis
• Papilledema
• Right pupil 5?4 mm, sluggish
• Left pupil 5?3 mm, brisk
• Extraocular movements intact
• Cranial Nerves otherwise intact

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Patient J.P.

• Motor exam
• Normal tone
• Follows simple commands intermittently
• Squeezes hands, wiggles toes
• Diffusely weak in all extremities
• Sensory Exam
• Sensation intact to light touch in all
  extremities
• Reflexes
• Reflexes 2, symmetrical
• No Hoffmans sign
• Toes downgoing
• Cerebellar/Gait exam
• Mild dysmetria bilaterally on finger-nose test
• Gait Deferred

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CT Scan
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Initial Management

• Patient transferred to LAC Medical Center
• Right ventriculostomy placed
• CSF sent for cytology ? atypical cells
• Patients exam significantly improved
• Awake, alert
• Oriented to name only (San Dimas , 1993)
• Significant short-term memory deficits
• Partial right IIIrd nerve palsy improved
• No pronator drift, power 5/5 throughout

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CT Scan
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MRI Brain
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Surgery

• Right interhemispheric transcallosal approach to
  third ventricle
• Patients right side down
• Frozen pathology ? malignant glial tumor with
  high cellularity
• Gross total resection

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Transcallosal Approach to the Third Ventricle

• Position with head in lateral position to allow
  gravity to facilitate in retraction
• Bone flap 2/3 anterior to coronal suture and 1/3
  posterior to coronal suture
• May modify accordingly for anterior versus
  posterior third ventricular lesions
• Callosal incision between 2 ACAs
• Must account for shift involved with lateral
  positioning
• Callosotomy approximately 2-3 cm in length
• Some authors advocate transverse callosotomy

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Video
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Postoperative MRI Brain
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Postoperative Course

• Patient with unchanged neurological status
  following procedure
• Ventriculostomy left in place yet unable to wean
  off
• Left VP shunt placed on postoperative day 7
• Short term memory slightly improved over course
  of week
• Patient transferred to step-down

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Pathology
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DiagnosisIntraventricular Anaplastic
Oligodendroglioma (WHO Grade III)
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Oligodendroglioma Background

• Two recognized grades
• WHO grade II oligodendroglioma
• WHO grade III anaplastic oligodendroglioma
• 4 of all primary brain tumors
• Mean age approximately 43 years
• 6 during infancy and childhood
• No known patterns of inheritance
• Most commonly occur in white matter of frontal
  and temporal lobes
• Intraventricular oligodendroglioma
• Approximately 20 case reports in the literature

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Anaplastic Oligodendroglioma Epidemiology

• Account for 3 of all adult supratentorial
  primary malignant gliomas
• Account for 20-54 of all oligodendrogliomas
• Most common in adults (mean age 49 years)
• Older than patients with grade II
  oligodendrogliomas
• Male to female ratio 1.5 1
• Preference for frontal lobe (60) followed by
  temporal lobe (33)

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Anaplastic Oligodendroglioma Histopathology

• Share with oligodendroglioma
• Honeycomb appearance with clear cytoplasm
• Fried egg yolk appearance
• Frequent calcification
• Occasional gemistocytes
• Often GFAP and S-100 positive
• Perinuclear halos
• Diffuse features of malignancy
• Increased cellularity
• Cellular atypia
• High mitotic index
• Necrosis and microvascular proliferation may be
  present
• Occasional multinucleated giant cells of Zulch

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Anaplastic Oligodendroglioma Differential
Diagnosis

• All with neoplastic cells with round nucleus and
  clear cytoplasm (oligodendroglioma-like cells or
  OLCs)
• Clear cell ependymoma
• ependymal features (ie rosettes) help
  differentiate
• Central neurocytoma
• Synaptophysin positive, more commonly originates
  in ventricles
• Clear cell meningioma
• PAS positive, EMA immunoreactivity
• Metastatic renal cell tumor

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Oligodendroglioma Molecular Genetics

• Chromosome 19
• Loss of heterozygosity (LOH) on long arm of
  chromosome 19 (19q)
• 50-80 of cases
• Chromosome 1
• LOH on short arm (1p) in 67 of cases
• Almost always coexists with LOH at 19q
• Polysomia, deletions on other chromosomes (ie
  9,10)
• Progression to malignancy correlates with EGFR,
  PDGF overexpression
• Fluorescence In Situ Hybridization (FISH) used to
  detect
• Lack of correlation between histology and
  molecular markers

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Oligodendroglioma Molecular genetics

• Several molecular subtypes
• 1) Combined/isolated loss of 1p/19q
• More likely frontal, parietal
• Diffuse enhancement
• Close to 100 response rate
• Survival greater than 10 years
• 2) 1p loss without 19q loss
• Close to 100 response rate
• Survival approximately 6 years
• 3) No deletion of 1p/19q with TP53 mutation
• More likely temporal, insular
• Ringe enhancement more likely
• 33 response rate
• Survival approximately 6 years
• 4) No deletion of 1p/19q, no TP53 mutation, yet
  other mutations
• 18 response rate
• Survival generally less than 18 months

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Anaplastic Oligodendroglioma Multimodal treatment

• Surgery is still primary treatment
• Gross total resection whenever possible
• Mixed data regarding adjuvant radiotherapy
• Postoperative radiation therapy has been shown to
  extend survival, yet carries associated morbidity
• Delayed XRT as effective as immediate postop XRT
  in one study
• Another study showed no benefit to radiotherapy
• XRT/chemo current standard in recurrent,
  high-grade oligodendroglioma
• Salvage therapy frequently chemotherapy with stem
  cell rescue

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Anaplastic Oligodendroglioma Response to
chemotherapy

• Tumors with combined 1p and 19q deletions are
  often responsive to chemotherapy
• Procarbazine, CCNU, Vincristine (PCV)
• Many side effects including myelosuppression in
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• More recently, temozolamide (in trials)
• Half of such tumors show complete radiological
  responses to chemotherapy
• Mean survival time 10 years with these deletions
  compared to patients without these deletions
  (mean 2 years)

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Anaplastic Oligodendroglioma Prognosis

• Median survival time of 4 years
• Five year survival 41
• Ten year survival 20
• Local tumor recurrence occurs frequently
• Leptomeningeal spreading (oligodendrogliomatosis
  ) has also been described
• Metastatic disease uncommon, yet incidence may be
  increasing
• Most common sites bone, lymph nodes, scalp
• Good prognostic factors
• Younger patient age
• Female sex
• Seizure as presenting symptom

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References

• 1. Merrell R et al. 1p/19q chromosome deletions
  in metastatic oligodendroglioma. J Neurooncology.
  2006
• 2. Waldron JS, Tihan T. Epidemiology and
  pathology of intraventricular tumors.
  Neurosurgery Clinical of N America. 14 (2003)
  469-482
• 3. Dumont AS et al. Intraventricular gliomas.
  Neurosurgery Clinical of N America. 14 (2003)
  571-591
• 4. Reifenberger G. Anaplastic oligodendroglioma.
  In Tumours of the Nervous System. (Kleihues P,
  Cavanee WK, eds.) IARC Press, 2000.
• 5. Kasowski HJ et al. Transcallosal
  Transchoroidal Approach to Tumors of the Third
  Ventricle. Neurosurgery 57, Suppl 3. 361-366,
  2005
• 6. Engelhard HH. Current diagnosis and treatment
  of Oligodendroglioma. Neurosurgical Focus. 12(2),
  2002.

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Thank You